Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS

Background Decreased but measurable serum IgA levels (≤70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD. This study tested the hypothesis that subnormal serum IgA levels would be associated with exacerbation risk in COPD. Methods Data were analyzed from 1,049 COPD participants from the observational cohort study SPIROMICS (535 (51%) women; mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA measured using the Myriad RBM biomarker discovery platform. Exacerbation data was collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear, logistic and zero-inflated negative binomial regressions were performed. Results Mean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum IgA (<7 mg/dL) and 25 (2.4%) had IgA level ≤70 mg/dL. Participants with IgA ≤70 mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those with higher IgA. In adjusted models, IgA ≤70 mg/dL was associated with higher exacerbation incidence rates (IRR 1.71, 95% CI 1.01–2.87, p = 0.044) and greater risk for any severe exacerbation (OR 2.99, 95% CI 1.30–6.94, p = 0.010). In adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL decrement in IgA (analyzed continuously) was associated with more exacerbations during follow-up (β 0.24, 95% CI 0.017–0.46, p = 0.035). Conclusions Subnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity. Additionally, a dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk. Future COPD studies should more comprehensively characterize immune status to define the clinical relevance of these findings and their potential for therapeutic correction.

[1]  J. W. Lee,et al.  Secretory IgA Deficiency in Individual Small Airways Is Associated with Persistent Inflammation and Remodeling , 2017, American journal of respiratory and critical care medicine.

[2]  J. Newell,et al.  Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD) , 2017, PloS one.

[3]  Meilan K. Han,et al.  Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts , 2017, American journal of respiratory and critical care medicine.

[4]  L. Gleaves,et al.  Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency , 2016, Nature Communications.

[5]  S. Hawken,et al.  A Retrospective Longitudinal Within-Subject Risk Interval Analysis of Immunoglobulin Treatment for Recurrent Acute Exacerbation of Chronic Obstructive Pulmonary Disease , 2015, PloS one.

[6]  R. Peng,et al.  Obesity as a susceptibility factor to indoor particulate matter health effects in COPD , 2015, European Respiratory Journal.

[7]  Meilan K. Han,et al.  Comparison of serum, EDTA plasma and P100 plasma for luminex-based biomarker multiplex assays in patients with chronic obstructive pulmonary disease in the SPIROMICS study , 2014, Journal of Translational Medicine.

[8]  Lisa M LaVange,et al.  Design of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) , 2013, Thorax.

[9]  J. W. Lee,et al.  Bronchial secretory immunoglobulin a deficiency correlates with airway inflammation and progression of chronic obstructive pulmonary disease. , 2011, American journal of respiratory and critical care medicine.

[10]  D. Schuppan,et al.  Serum IgA in Celiac Disease: The Unrecognized Importance of Partial IgA Deficiency , 2011 .

[11]  A. Hildesheim,et al.  Determinants and Correlation of Systemic and Cervical Concentrations of Total IgA and IgG , 2009, Cancer Epidemiology, Biomarkers & Prevention.

[12]  D. Furst.  Serum immunoglobulins and risk of infection: how low can you go? , 2009, Seminars in arthritis and rheumatism.

[13]  F. Gudé,et al.  Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities , 2007, Clinical and experimental immunology.

[14]  M. Kerr,et al.  The clinical significance of immunoglobulin A deficiency , 2007, Annals of clinical biochemistry.

[15]  L. Fabbri,et al.  Pathophysiology of exacerbations of chronic obstructive pulmonary disease. , 2006, Proceedings of the American Thoracic Society.

[16]  S. Durham,et al.  Mucosal immunity in asthma and chronic obstructive pulmonary disease: a role for immunoglobulin A? , 2012, Proceedings of the American Thoracic Society.

[17]  M. Stenzel,et al.  Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians , 2004, European journal of clinical investigation.

[18]  C. Cunningham-Rundles,et al.  Common variable immunodeficiency: clinical and immunological features of 248 patients. , 1999, Clinical immunology.

[19]  D. Webb,et al.  Selective Immunoglobulin A Deficiency and Chronic Obstructive Lung Disease: A Family Study , 1974 .